Dynamic assembly of the calcium hemostasis modulator 1 channel gates ATP permeation

Calcium hemostasis modulator 1 (CALHM1) is a voltage- and Ca2+-gated ATP channel that plays an important role in neuronal signaling. The currently reported CALHM structures are all in an ATP-conducting state, and the gating mechanism of ATP permeation remains elusive. Here, we report three cryo-EM reconstructions of heptameric CALHM1s with ordered or flexible long C-terminal helices and octameric CALHM1 with flexible long C-terminal helices at resolutions of 3.2 Å, 2.9 Å, and 3.5 Å. Structural analysis revealed that the heptameric CALHM1s are in an ATP nonconducting state in which the pore diameter in the middle is approximately 6.6 Å. Compared with those inside the octameric CALHM1s, the N-helices inside heptameric CALHM1s are in the "down" position to avoid steric clash with neighboring TM1 helices. MD simulations show that the pore size is significantly increased for ATP permeation during the movement of the N-helix from the "down" position to the "up" position. Therefore, we proposed a mechanism in which the "piston-like" motion of the N-helix drives the dynamic assembly of the CALHM1 channel for ATP permeation.

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Structure of the full-length human Pannexin1 channel and insights into its role in pyroptosis

Cell Discovery ◽

10.1038/s41421-021-00259-0 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sensen Zhang ◽

Baolei Yuan ◽

Jordy Homing Lam ◽

Jun Zhou ◽

Xuan Zhou ◽

...

Keyword(s):

Md Simulation ◽

Potential Role ◽

Md Simulations ◽

Full Length ◽

Inflammasome Activation ◽

Simulation Studies ◽

Cryo Electron Microscopy ◽

Gating Mechanism ◽

Atp Efflux

AbstractPannexin1 (PANX1) is a large-pore ATP efflux channel with a broad distribution, which allows the exchange of molecules and ions smaller than 1 kDa between the cytoplasm and extracellular space. In this study, we show that in human macrophages PANX1 expression is upregulated by diverse stimuli that promote pyroptosis, which is reminiscent of the previously reported lipopolysaccharide-induced upregulation of PANX1 during inflammasome activation. To further elucidate the function of PANX1, we propose the full-length human Pannexin1 (hPANX1) model through cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulation studies, establishing hPANX1 as a homo-heptamer and revealing that both the N-termini and C-termini protrude deeply into the channel pore funnel. MD simulations also elucidate key energetic features governing the channel that lay a foundation to understand the channel gating mechanism. Structural analyses, functional characterizations, and computational studies support the current hPANX1-MD model, suggesting the potential role of hPANX1 in pyroptosis during immune responses.

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Porous Characteristics of Three-Dimensional Disordered Graphene Networks

Crystals ◽

10.3390/cryst11020127 ◽

2021 ◽

Vol 11 (2) ◽

pp. 127

Author(s):

YongChao Wang ◽

YinBo Zhu ◽

HengAn Wu

Keyword(s):

Pore Size ◽

Low Temperatures ◽

Gas Adsorption ◽

Three Dimensional ◽

Md Simulations ◽

Structural Features ◽

Atomic Scale ◽

Critical Factors ◽

Chlorination Process ◽

Porous Morphology

The porous characteristics of disordered carbons are critical factors to their performance on hydrogen storage and electrochemical capacitors. Even though the porous information can be estimated indirectly by gas adsorption experiments, it is still hard to directly characterize the porous morphology considering the complex 3D connectivity. To this end, we construct full-atom disordered graphene networks (DGNs) by mimicking the chlorination process of carbide-derived carbons using annealing-MD simulations, which could model the structure of disordered carbons at the atomic scale. The porous characteristics, including pore volume, pore size distribution (PSD), and specific surface area (SSA), were then computed from the coordinates of carbon atoms. From the evolution of structural features, pores grow dramatically during the formation of polyaromatic fragments and sequent disordered framework. Then structure is further graphitized while the PSD shows little change. For the obtained DGNs, the porosity, pore size, and SSA increase with decreasing density. Furthermore, SSA tends to saturate in the low-density range. The DGNs annealed at low temperatures exhibit larger SSA than high-temperature DGNs because of the abundant free edges.

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Diffusion of Heavy Oil in SiO2 Model Catalyst and FCC Catalyst

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.550-553.158 ◽

2012 ◽

Vol 550-553 ◽

pp. 158-163 ◽

Cited By ~ 2

Author(s):

Zi Yuan Liu ◽

Sheng Li Chen ◽

Peng Dong ◽

Xiu Jun Ge

Keyword(s):

Diffusion Coefficient ◽

Pore Size ◽

Effective Diffusion Coefficient ◽

Pore Diameter ◽

Effective Diffusion ◽

Model Catalyst ◽

Average Pore ◽

Diffusion Factor ◽

Fcc Catalyst ◽

Fcc Catalysts

Through the measured effective diffusion coefficients of Dagang vacuum residue supercritical fluid extraction and fractionation (SFEF) fractions in FCC catalysts and SiO2model catalysts, the relation between pore size of catalyst and effective diffusion coefficient was researched and the restricted diffusion factor was calculated. The restricted diffusion factor in FCC catalysts is less than 1 and it is 1~2 times larger in catalyst with polystyrene (PS) template than in conventional FCC catalyst without template, indicating that the diffusion of SFEF fractions in the two FCC catalysts is restricted by the pore. When the average molecular diameter is less than 1.8 nm, the diffusion of SFEF fractions in SiO2model catalyst which average pore diameter larger than 5.6 nm is unrestricted. The diffusion is restricted in the catalyst pores of less than 8 nm for SFEF fractions which diameter more than 1.8 nm. The tortuosity factor of SiO2model catalyst is obtained to be 2.87, within the range of empirical value. The effective diffusion coefficient of the SFEF fractions in SiO2model catalyst is two orders of magnitude larger than that in FCC catalyst with the same average pore diameter. This indicate that besides the ratio of molecular diameter to the pore diameter λ, the effective diffusion coefficient is also closely related to the pore structure of catalyst. Because SiO2model catalyst has uniform pore size, the diffusion coefficient can be precisely correlated with pore size of catalyst, so it is a good model material for catalyst internal diffusion investigation.

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Valine-279 Deletion–Mutation on Arginine Vasopressin Receptor 2 Causes Obstruction in G-Protein Binding Site: A Clinical Nephrogenic Diabetes Insipidus Case and Its Sub-Molecular Pathogenic Analysis

Biomedicines ◽

10.3390/biomedicines9030301 ◽

2021 ◽

Vol 9 (3) ◽

pp. 301

Author(s):

Ming-Chun Chen ◽

Yu-Chao Hsiao ◽

Chun-Chun Chang ◽

Sheng-Feng Pan ◽

Chih-Wen Peng ◽

...

Keyword(s):

Structural Analysis ◽

Protein Binding ◽

Diabetes Insipidus ◽

Binding Site ◽

G Protein ◽

Arginine Vasopressin ◽

Nephrogenic Diabetes Insipidus ◽

Md Simulations ◽

Protein Binding Site ◽

Vasopressin Receptor

Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 (AVPR2) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified AVPR2 mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis. The patient was identified to have a valine 279 deletion–mutation in the AVPR2 gene. Cellular experiments using mutant protein transfected cells revealed that mutated AVPR2 is expressed successfully in cells and localized on cell surfaces. We further analyzed the pathogenesis of the mutation at sub-molecular levels via long-term molecular dynamics (MD) simulations and structural analysis. The MD simulations showed while the structure of the extracellular ligand-binding domain remains unchanged, the mutation alters the direction of dynamic motion of AVPR2 transmembrane helix 6 toward the center of the G-protein binding site, obstructing the binding of G-protein, thus likely disabling downstream signaling. This study demonstrated that the computational approaches can be powerful tools for obtaining valuable information on the pathogenesis induced by mutations in G-protein-coupled receptors. These methods can also be helpful in providing clues on potential therapeutic strategies for CNDI.

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Prediction of Fluid Flow in Artificial Cancellous Bone

Applied Mechanics and Materials ◽

10.4028/www.scientific.net/amm.695.393 ◽

2014 ◽

Vol 695 ◽

pp. 393-397

Author(s):

Elsa Syuhada Abdull Yamin ◽

Nor Azwadi Che Sidik

Keyword(s):

Fluid Flow ◽

Pore Size ◽

Surface Area ◽

Pore Diameter ◽

Bone Surface ◽

Flow Conditions ◽

Morphological Aspects ◽

Flow Through ◽

Structure Result ◽

Dynamics Method

The permeability of the blood in the artificial cancellous are affected by certain morphological aspects that include pore diameter, pore size, porosity and the bone surface area. In this study, computational fluid dynamics method is used to study the fluid flow through the cancellous structure. Result of the present work show that geometries with the same porosity and overall volume can have different permeability due to the differences in bone surface area. The hexahedron geometry has the highest permeability under stimulated blood flow conditions, where the cylindrical geometry has the lowest. Linear relationship is found between permeability and the two physical properties, bone surface area and the pore size.

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SBA-15 with Crystalline Walls Produced via Thermal Treatment with the Alkali and Alkali Earth Metal Ions

Materials ◽

10.3390/ma14185270 ◽

2021 ◽

Vol 14 (18) ◽

pp. 5270

Author(s):

Sung Soo Park ◽

Sang-Wook Chu ◽

Liyi Shi ◽

Shuai Yuan ◽

Chang-Sik Ha

Keyword(s):

Metal Ions ◽

Pore Size ◽

Metal Ion ◽

Pore Diameter ◽

Earth Metal ◽

Silica Matrix ◽

Alkali Earth Metal ◽

Alkali Earth ◽

Large Pore ◽

Large Pore Size

Crystalline walled SBA-15 with large pore size were prepared using alkali and alkali earth metal ions (Na+, Li+, K+ and Ca2+). For this work, the ratios of alkali metal ions (Si/metal ion) ranged from 2.1 to 80, while the temperatures tested ranged from 500 to 700 °C. The SBA-15 prepared with Si/Na+ ratios ranging from 2.1 to 40 at 700 °C exhibited both cristobalite and quartz SiO2 structures in pore walls. When the Na+ amount increased (i.e., Si/Na increased from 80 to 40), the pore size was increased remarkably but the surface area and pore volume of the metal ion-based SBA-15 were decreased. When the SBA-15 prepared with Li+, K+ and Ca2+ ions (Si/metal ion = 40) was thermally treated at 700 °C, the crystalline SiO2 of quartz structure with large pore diameter (i.e., 802.5 Å) was observed for Ca+2 ion-based SBA-15, while no crystalline SiO2 structures were observed in pore walls for both the K+ and Li+ ions treated SBA-15. The crystalline SiO2 structures may be formed by the rearrangement of silica matrix when alkali or alkali earth metal ions are inserted into silica matrix at elevated temperature.

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Regulation of functional nuclear pore size in fibroblasts

Journal of Cell Science ◽

10.1242/jcs.114.24.4621 ◽

2001 ◽

Vol 114 (24) ◽

pp. 4621-4627

Author(s):

Carl M. Feldherr ◽

Debra Akin ◽

Robert J. Cohen

Keyword(s):

Pore Size ◽

Transcriptional Activation ◽

Pore Diameter ◽

Nuclear Transport ◽

Control Level ◽

Proteasome Inhibitors ◽

Nuclear Pore ◽

Transport Capacity ◽

3T3 Cells ◽

Gold Particles

Protein-NLS-coated gold particles up to approximately 250 Å in diameter are transported through the nuclear pores in normal, proliferating BALB/c 3T3 cells. This size can increase or decrease, depending on cellular activity. It has been suggested that increases in functional pore size are related to a reduction in the amount of available p53. To further test this hypothesis, we investigated the effects of cycloheximide and pifithrin-α, which inhibits p53-dependent transcriptional activation, on nuclear transport. After 3 hours in cycloheximide, there was a significant increase in the size of the gold particles that entered the nucleoplasm. When the incubation period was extended to 6 hours or longer, transport capacity returned to the control level. By using proteasome inhibitors, it was shown that the cycloheximide-dependent increase in functional pore size was due to the inhibition of protein synthesis, consistent with the fact that p53 is a short-lived protein, and requires the activity of at least two different factors. Although cycloheximide increases the functional diameter of the channel available for signal-mediated transport by approximately 60 Å, it had no significant effect on either the import rate of small NLS-containing substrates (FITC-BSA-NLS), or passive diffusion of fluorescent-labeled proteins across the envelope. This suggests that changes in transport capacity were not caused by an increase in overall pore diameter but instead are due to a transient increase in pore size that accompanies signal-mediated transport. Pifithrin-α also caused an increase in functional pore diameter without altering the import rate of FITC-BSA-NLS, providing further support for the view that p53 can initiate changes in nuclear transport capacity.

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Investigations of the Mechanical and Hydrothermal Stabilities of SBA-15 and Al-SBA-15 Mesoporous Materials

MRS Advances ◽

10.1557/adv.2016.499 ◽

2016 ◽

Vol 1 (35) ◽

pp. 2453-2458 ◽

Cited By ~ 1

Author(s):

Dayton G. Kizzire ◽

James Thomas ◽

Sonal Dey ◽

Hayley Osman ◽

Robert A. Mayanovic ◽

...

Keyword(s):

Molecular Dynamics ◽

Pore Size ◽

Mesoporous Materials ◽

High Surface ◽

Md Simulations ◽

High Energy ◽

Hydrothermal Stability ◽

Synchrotron Source ◽

Stability Properties

ABSTRACTPeriodic mesoporous materials possess high surface to volume ratio and nano-scale sized pores, making them potential candidates for heterogeneous catalysis, ion exchange, gas sensing and other applications. In this study, we use in situ small angle x-ray scattering (SAXS) and molecular dynamics (MD) simulations to investigate the mechanical and hydrothermal stability properties of periodic mesoporous SBA-15 silica and SBA-15 type aluminosilica (Al-SBA-15) to extreme conditions. The mesoporous SBA-15 silica and Al-SBA-15 aluminosilica possess amorphous frameworks and have similar pore size distribution (pore size ∼9-10 nm). The in situ SAXS measurements were made at the B1 beamline, at the Cornell High Energy Synchrotron Source (CHESS). The mesoporous SBA-15 silica and Al-SBA-15 aluminosilica specimens were loaded in a diamond anvil cell (DAC) for pressure measurements, and, separately, with water in the DAC for hydrothermal measurements to high P-T conditions (to 255 °C and ∼ 114 MPa). Analyses of the pressure-dependent SAXS data show that the mesoporous Al-SBA-15 aluminosilica is substantially more mechanically stable than the SBA-15 silica. Hydrothermal measurements show a small net swelling of the framework at elevated P-T conditions, due to dissolution of water into the pore walls. Under elevated P-T conditions, the Al-SBA-15 aluminosilica shows significantly greater hydrothermal stability than the SBA-15 silica. Our MD simulations show that the bulk modulus value of periodic mesoporous SBA-15 silica varies exponentially with percentage porosity. Molecular dynamics simulations are being made in order to better understand how the pore architecture and the chemical composition of the host structure govern the stability properties of the mesoporous materials.

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Evaluation of Optimal Pore Size of (3-Aminopropyl)triethoxysilane Grafted MCM-41 for Improved CO2Adsorption

Journal of Chemistry ◽

10.1155/2015/608265 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Zhilin Liu ◽

Yang Teng ◽

Kai Zhang

Keyword(s):

Pore Size ◽

Pore Diameter ◽

High Energy ◽

Mesopore Volume ◽

Average Pore ◽

Major Drawback ◽

Swelling Agent ◽

Adsorption Capacities ◽

Structural Regularity ◽

Mcm 41

An array of new MCM-41 with substantially larger average pore diameters was synthesized through adding 1,3,5-trimethylbenzene (TMB) as the swelling agent to explore the effect of pore size on final adsorbent properties. The pore expanded MCM-41 was also grafted with (3-Aminopropyl)triethoxysilane (APTES) to determine the optimal pore size for CO2adsorption. The pore-expanded mesoporous MCM-41s showed relatively less structural regularity but significant increments of pore diameter (4.64 to 7.50 nm); the fraction of mesopore volume also illustrated an increase. The adsorption heat values were correlated with the order of the adsorption capacities for pore expanded MCM-41s. After amine functionalization, the adsorption capacities and heat values showed a significant increase. APTES-grafted pore-expanded MCM-41s depicted a high potential for CO2capture regardless of the major drawback of the high energy required for regeneration.

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Fabrication of Porous SiAlON Using Fe2O3 as Pore Former

Materials Science Forum ◽

10.4028/www.scientific.net/msf.804.267 ◽

2014 ◽

Vol 804 ◽

pp. 267-270

Author(s):

Qing Wen Duan ◽

Rong Zhen Liu ◽

Hai Yun Jin ◽

Jian Feng Yang ◽

Zhi Hao Jin

Keyword(s):

Particle Size ◽

Porous Materials ◽

Pore Size ◽

Fracture Mode ◽

Size Effects ◽

Pore Diameter ◽

Bending Strength ◽

Thermal Reduction ◽

Pore Former ◽

Median Pore

Porous SiAlON ceramics were fabricated by carbo-thermal reduction nitridation method using Fe2O3 as pore former. Particle size effects of Fe2O3 were reported in this paper. The results showed that composites were composed by SiAlON, AlN and Iron Silicon phases. The median pore diameter of Sialon was affected by the composition and particle size of Fe2O3. The fracture mode of this material was intergranular. With the increase of Fe2O3 additions, the porosity of this materials increased. The bending strength of this material was reversely proportional to Fe2O3 particle size. The maximum bending strength of Porous materials with 30wt.% Fe2O3 additions (with a porosity about 65% and the pore size is about 1μm) could reach 22 MPa. The porous Sialon ceramics with a smaller pore size exhibited a higher bending strength.

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